Patients with type 2 diabetes who had proteinuria and systolic blood pressure less than 130 mm Hg had a higher risk of cardiovascular
and total mortality than those with higher blood pressure and no proteinuria, a study found. More...

Drug-eluting stents better, safer than bare metal in diabetics

Any drug-eluting stent was safer and more efficacious than bare metal stents in diabetics, with the everolimus-eluting stent
appearing to have the best results, a meta-analysis found. More...

Test yourself

MKSAP Quiz: Treatment plan for prediabetes

This month's quiz asks readers to evaluate a 68-year-old woman with a fasting plasma glucose level of 113 mg/dL. More...

Among elective surgery patients, nearly one-fourth (24%) were diagnosed with previously unknown diabetes or prediabetes based
on blood tests conducted while they were fasting preoperatively, researchers found. More...

Clopidogrel associated with decreased benefit in diabetics post-MI

Diabetics benefit less from receiving clopidogrel after myocardial infarction than non-diabetics, a study found. More...

From ACP Internist

Teaching diabetes self-management 'basic survival skills'

Diabetes self-management education is a cost-efficient, effective treatment that is underused in the United States, according
to speakers at the 2012 annual meeting of the American Diabetes Association. More...

Tool of the month

Advice on reimbursement for group visits

If physicians, midlevel providers, or nurses participate in the group visits, they can be reimbursed in exactly the same way
as they would be for individual appointments. More...

FDA update

New weight loss drug approved

Lorcaserin hydrochloride (Belviq) was recently approved by the FDA for chronic weight management in adults. More...

Keeping tabs

Spotlight on viruses and diabetes

The possible role of viruses in the development of diabetes was analyzed by two recent studies. More...

Researchers recruited patients from nine diabetes clinics in Italy to assess insulin secretion and action as well as cardiovascular
risk profile according to both HbA1c and the OGTT. Included patients, all of whom were considered at risk for type 2 diabetes,
had OGTTs done after fasting overnight and after not smoking for at least 12 hours. While patients were fasting, plasma glucose,
insulin, and C-peptide levels, lipid profile, and HbA1c were determined. Plasma glucose and C-peptide levels were then measured
again 15, 30, 60, 90 and 120 minutes after patients ingested a 75-g glucose load over a five-minute period. The researchers
compared patients' glucose regulation categories by the OGTT and HbA1c. The study results were published online Aug. 21 by Diabetes Care.

Eight hundred forty-four patients were included in the study. Forty-four percent were men, and the mean age was 49.5±12
years. Mean BMI was 29±5 kg/m2. OGTT identified that 42% of patients had impaired glucose regulation and 15% had a new diagnosis of type 2 diabetes mellitus
based on the American Diabetes Association's 2003 criteria. The HbA1c level found that 38% of patients had prediabetes (HbA1c
5.7%-6.4%) and 11% had type 2 diabetes (HbA1c ≥6.5%). The respective concordance rates were 54% and 44%.

Patients who had prediabetes on both tests had more insulin resistance, more impaired insulin secretion, and a worse cardiovascular
risk profile than patients whose glucose tolerance was normal on both tests. The researchers performed logistic regression
analyses adjusted for age, sex, and body mass index and found that patients with prediabetes or type 2 diabetes diagnosed
with the OGTT versus HbA1c had a higher risk for insulin resistance and impaired insulin secretion.

The researchers pointed out that each diagnostic test was performed only once. In addition, they did not assess patients for
factors that can affect HbA1c levels, such as anemia (which can falsely lower HbA1c), and the study participants did not represent
the general population because they were recruited based on their increased risk for type 2 diabetes. The authors concluded
that HbA1c level is a less sensitive test and identifies fewer patients with prediabetes and even fewer patients with type
2 diabetes when compared with the OGTT. Patients who were characterized as having prediabetes or type 2 diabetes on both tests
had worse metabolic profiles. Insulin resistance, insulin secretion and cardiovascular risk profile did not differ between
tests in patients identified as having prediabetes, the researchers noted.

"Our findings are in agreement with those observed in other Caucasian populations…and confirm that HbA1c is a specific
but insensitive method for diagnosis of [type 2 diabetes mellitus] or prediabetes," they wrote.

Patients with type 2 diabetes who had proteinuria and systolic blood pressure (BP) less than 130 mm Hg had a higher risk of
cardiovascular and total mortality than those with higher blood pressure and no proteinuria, a study found.

Researchers prospectively followed 881 Finnish patients with type 2 diabetes, aged 45 to 64 years, for 18 years. Patients
were excluded if they had type 1 diabetes, had possible or definite stroke or myocardial infarction, or had lower-extremity
amputation at baseline examination. They were categorized into four groups based on systolic BP at baseline: <130 mm
Hg, 130-139 mm Hg, 140-159 mm Hg, and ≥160 mm Hg. They were then stratified as having no proteinuria (≤150 mg/L)
or borderline/clinical proteinuria (>150 mg/L). Study endpoints were total mortality, cardiovascular disease (CVD) mortality
and coronary heart disease (CHD) mortality. Researchers used a Cox proportional hazards model to evaluate the effect of systolic
BP in the different proteinuria groups on mortality, using the <130 mm Hg group as the reference. Results were published online August 24 by the Journal of General Internal Medicine.

Sixty-nine percent (n=607) of patients died during follow-up, including 44.8% (n=395) from CVD. There was a statistically significant interaction between proteinuria and baseline systolic BP (P=0.01) for total mortality as well as for CVD mortality (P=0.05). The interaction for CHD mortality wasn't significant. After adjustment for confounders, patients with proteinuria
and systolic BP <130 mm Hg had about twice the risk of total and CVD mortality as those with BP between 130 and 139 mm
Hg (P<0.05), and about 1.6 times greater total and CVD mortality as those with systolic BP between 140 and 159 mm Hg. CVD
mortality was also 1.6 times higher (P<0.05) in those with systolic BP <130 mm Hg versus those with systolic BP ≥160 mm Hg. In patients without proteinuria,
a systolic BP <130 mm Hg was associated with a statistically nonsignificant decrease in total and CVD mortality.

In diabetic patients with proteinuria, systolic BP below 130 mm Hg may be a marker of underlying disease, the authors wrote.
The results suggest "it might be justifiable to recommend higher systolic BP targets for patients with type 2 diabetes and
proteinuria compared to those without proteinuria," they wrote. Limitations that affect the generalizability of this study
include that the baseline exam occurred from 1982-1984, blood pressure was only obtained at baseline with no follow-up, patients'
baseline hemoglobin A1c was 9.9%, and there was no information about what antihypertensives (including ACE inhibitors) were
taken during the study.

All drug-eluting stents were associated with a reduction in target vessel revascularization, ranging from 37% to 69%. Everolimus-eluting
stents performed about the same as sirolimus-eluting stents. These two stents had lower rates than paclitaxel-eluting stents
or zotarolimus-eluting stents, and all four did better than bare metal stents.

There was about an 87% probability that everolimus-eluting stents were the most efficacious, the authors reported. The median
target vessel revascularization rate with bare metal stents was 109.40 per 1,000 patient-years of follow-up, and the rate
with the everolimus-eluting stent was 34.55 per 1,000 patient-years.

There was no increased risk of any safety outcome, including very late stent thrombosis, with any drug-eluting stents compared
with bare metal stents, the researchers reported. There was about a 62% probability that the everolimus-eluting stent was
the safest stent on the outcome of stent thrombosis, a 57% probability that everolimus-eluting stents were associated with
the lowest death rate, and an 81% probability that everolimus-eluting stents had the lowest rate of myocardial infarction.

"In patients with diabetes all drug eluting stents are highly efficacious at reducing the risk of target vessel revascularization
without increases in any adverse safety outcomes, including very late stent thrombosis, when compared with bare metal stents,"
the authors concluded. "There were significant differences among types of drug eluting stent for efficacy and safety, such
that everolimus eluting stents were the most efficacious and safe."

Using a random-effects model, the review authors found that patients treated to intensive targets did not significantly differ
from standard-targeted patients in their rates of mortality (relative risk [RR], 0.76; 95% CI, 0.55 to 1.05) or myocardial
infarction (RR, 0.93; 95% CI, 0.80 to 1.08). The intensive targets were associated with a decrease in the risk of stroke (RR,
0.65; 95% CI, 0.48 to 0.86). A pooled analysis of risk differences showed only a small absolute decrease in stroke risk (absolute
risk, −0.01; 95% CI, −0.02 to −0.00) and no effect on mortality or myocardial infarction.

The researchers also looked at the benefits of standard blood pressure targets compared to historical treatment, defined as
a blood pressure target higher than standard targets or as treatment in which a placebo or usual care was provided, and observed
a much greater difference than they found between standard and intensive treatment. The number needed to treat to achieve
benefit with intensive treatment is threefold what it is for standard treatment compared to historical treatment, they calculated.
They concluded that intensive blood pressure targets do not appear to reduce the risk of mortality or myocardial infarction.

Current guidelines recommend targets of 130/80 mm Hg or less for patients with type 2 diabetes, the authors noted. Based on
the review, they were not able to recommend a specific alternative target, but they suggested that their findings be considered
in future guideline development.

According to an accompanying commentary, future guidelines are likely to suggest a target of 140/90 mm Hg or less.

"Physicians need to understand and discuss these goals with their patients," the commentary authors concluded.

Among elective surgery patients, nearly one-fourth (24%) were diagnosed with previously unknown diabetes or prediabetes based
on blood tests conducted while they were fasting preoperatively, researchers found.

To assess whether diabetes testing could be incorporated into the elective surgical work-up, researchers conducted a prospective
observational study among 275 patients undergoing elective total knee or hip arthroplasty or elective lumbar decompression
and/or fusion who had a preoperative visit between December 2007 and November 2008 at a large Wisconsin academic medical center.

The mean patient age was 60.3 years, and 88% had a body mass index greater than 25 kg/m2. All of the patients had insurance; 97% had a primary care clinician, and 96.6% of patients had seen a primary clinician
within the past year. Fasting blood glucose (FBG) was drawn immediately before surgery, and patients with preoperative FBG
greater than 100 mg/dL had another blood sample taken six to eight weeks postoperatively.

In the study, 18% of patients had known diabetes or prediabetes, and 58% were normoglycemic. The other 24% were found to have
previously unrecognized diabetes or impaired fasting glucose based on both preop FBG and follow-up FBG. Sixty-four percent
of patients with FBG greater than 100 mg/dL preoperatively still had an elevated value at their follow-up visit.

Researchers noted that with more than 1 million total knee and hip operations done in the U.S. annually, such screening could
potentially identify more than a quarter-million previously unknown cases of diabetes or prediabetes. Considering that 70
million patients undergo ambulatory or inpatient procedures each year, if one quarter of them allowed for easy preoperative
testing, then more than 4 million cases of diabetes and impaired fasting glucose could be found annually. Accountable care
organizations may encourage such novel interventions, the authors noted.

Researchers said, "Remarkably, this statistic [24%] likely represents a 'best case scenario,' as the percent of undiagnosed
patients is likely higher in uninsured patients, those without primary care visits, and those hospitalized for emergent or
urgent reasons who, by definition, did not have an ambulatory preoperative evaluation, and who may also have greater severity
of illness at baseline."

Clopidogrel associated with decreased benefit in diabetics post-MI

Diabetics benefit less from receiving clopidogrel after myocardial infarction (MI) than non-diabetics, a study found.

To estimate the clinical effectiveness associated with clopidogrel treatment after MI in patients with diabetes, Danish researchers
reviewed registry data for patients hospitalized for their heart attack who had survived 30 days after discharge and had not
undergone coronary artery bypass surgery.

Results appeared in the Sept. 5 Journal of the American Medical Association.

Of the 58,851 patients included in the study, 7,247 (12%) had diabetes and 35,380 (60%) received clopidogrel. In total, 1,790
patients (25%) with diabetes and 7,931 patients (15%) without diabetes met the composite end point of recurrent MI and all-cause
mortality.

In the overall study population, 978 patients with diabetes (80%) and 4,100 patients without diabetes (76%) died of cardiovascular
events. Diabetics who were treated with clopidogrel had an unadjusted mortality rate of 13.4 events per 100 person-years (95%
CI, 12.8 to 14.0 events per 100 person-years) compared to 29.3 events per 100 person-years (95% CI, 28.3 to 30.4 events per
100 person-years) for untreated diabetics. Non-diabetics treated with clopidogrel had unadjusted mortality rates of 6.4 events
per 100 person-years (95% CI, 6.3 to 6.6 events per 100 person-years) compared to 21.3 events per 100 person-years (95% CI,
21.0 to 21.7 events per 100 person-years) for those not treated.

no reduction in the composite end point in diabetics compared to non-diabetics (HR, 1.00 [95% CI, 0.91 to 1.10] vs. 0.91 [95%
CI, 0.87 to 0.96]; P for interaction, 0.08).

Although head-to-head trials are needed, the study authors speculated that based on other published data, "[P]rasugrel may
constitute an attractive alternative to clopidogrel in patients with diabetes with acute coronary syndromes, especially if
recurrent ischemic events have occurred during clopidogrel treatment."

An editorialist noted that evidence on the effects of various antiplatelet options in diabetics is still developing, but that it's clear these
patients face a higher risk of adverse events after MI. "At least a portion of this excess risk appears due to platelet activity
and function and to the effects of antiplatelet medications in patients with diabetes. Therefore, in appropriately selected
patients, intensification of the antiplatelet regimen may be one method by which their outcomes might be markedly improved,"
the editorial concluded.

From ACP Internist

Teaching diabetes self-management 'basic survival skills'

Diabetes self-management education is a cost-efficient, effective treatment that is underused in the United States, according
to speakers at the 2012 annual meeting of the American Diabetes Association (ADA).

Read the ADA conference coverage in the September ACP Internist to learn about new, evidence-based methods for teaching self-management in the hospital and outpatient practice.

Tool of the month

Advice on reimbursement for group visits

Group visits are a highly effective and efficient way to enhance diabetes management and self-management support.

If physicians, midlevel providers, or nurses participate in the group visits, they can be reimbursed in exactly the same way
as they would be for individual appointments. Just as in individual appointments, documentation must match the billing code
used. Vital signs and other routine data should be charted. Clinicians participating in the visit must create a progress note,
and an ICD-9 and CPT code for each patient service must be entered on an encounter form.

The following CPT codes are generally used for follow-up appointments conducted as group visits: 99212, 99213, 99214, and
(sometimes) 99215, depending on the level of service rendered. Several excellent resources provide step-by-step guidance in
planning and implementing a group visit for your patients with diabetes. One comprehensive guide is "The Group Visit Starter
Kit: Improving Chronic Illness Care," which is available free of charge online.

FDA update

New weight loss drug approved

Lorcaserin hydrochloride (Belviq) was recently approved by the FDA for chronic weight management in adults with a body mass
index (BMI) of 30 kg/m2 or greater, or adults with a BMI of 27 kg/m2 or greater who have at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia.

Safety and efficacy were evaluated in three trials of nearly 8,000 obese and overweight patients who received a reduced-calorie
diet and exercise counseling, according to an FDA press release. Compared with placebo, treatment for up to one year was associated with average weight loss of 3% to 3.7%. The most common
side effects are headache, dizziness, fatigue, nausea, dry mouth and constipation in non-diabetic patients and hypoglycemia,
headache, back pain, cough and fatigue in diabetic patients. The drug activates the serotonin C receptor and should not be
used during pregnancy. Treatment may cause serious side effects, including serotonin syndrome.

Keeping tabs

Spotlight on viruses and diabetes

The possible role of viruses in the development of diabetes was analyzed by two recent studies.

Researchers in Australia calculated the incidence of type 1 diabetes among children under age 15 between 1985 and 2010. Overall
incidence of the disease increased by an average of 2.3% per year, with a mean incidence of 18.1 per 100,000 person-years.
But the study also found a sinusoidal cyclical variation; there appeared to be a five-year cycle of peaks and troughs in diabetes incidence.
This cycle closely matches one that was previously observed in Northeast England, the researchers noted.

The cycles support the idea that environmental factors could play a role in type 1 diabetes development, according to the
brief report of the study, which was published online by Diabetes Care in July. Viral infections are one likely factor, although climate effects on lifestyle or other risk factors could be an alternative
explanation, the study authors said. They called for future research to identify the causative factors.

Viral infection has been previously suspected as a contributor to type 1 diabetes, but another recent study suggests that
cytomegalovirus (CMV) might also be a risk factor for type 2 diabetes in elderly patients. Researchers in the Netherlands
compared rates of type 2 diabetes and CMV infection among 600 people age 85 or older. Of the participants who were seropositive
for CMV, 17.2% had diabetes, compared to 7.9% of negative participants (P=0.016). The positive group also had higher hemoglobin A1c and nonfasting glucose, according to results published by Immunity and Ageing on Aug. 28.

The authors suggested a number of ways in which the viral infection could accelerate pancreatic failure, including directly
affecting the pancreatic cells or creating a pro-inflammatory environment in the immune system generally. They noted that
a significant association between CMV and type 2 diabetes had not been found in previous studies of younger patients, and
that it's possible CMV could be a result instead of a cause of diabetes. However, CMV is often acquired during childhood,
so that's unlikely to fully explain the association. The authors called for more research on the causality of their findings.

MKSAP Answer and Critique

The correct answer is B. Diet and exercise. This item is available to MKSAP 15 subscribers as item 21 in the Endocrinology
section. Part A of MKSAP 16 will be released on July 31. More information is available online.

This patient with impaired fasting glucose (IFG), defined as a fasting plasma glucose level in the range of 100 to 125 mg/dL
(5.6 to 6.9 mmol/L), should begin a program of intensive lifestyle change, including 30 minutes of exercise most days of the
week and a calorie-restricted diet, to achieve weight reduction on the order of 7% of body weight.

According to a consensus statement on the prevention of diabetes from the American Diabetes Association and the European Association
for the Study of Diabetes, diet and exercise is the recommended approach for patients with either IFG or impaired glucose
tolerance (IGT), the prediabetic states. In the Diabetes Prevention Program (DPP), the relative risk reduction (RRR) in the
incidence of diabetes in patients with IGT who were assigned to intensive lifestyle change was 58%.

Pharmacologic therapy with glucose-lowering drugs is not indicated for this patient with isolated IFG. In pharmacologic studies
of diabetes prevention, acarbose therapy resulted in only a 25% RRR, which is inferior to that obtained with diet and exercise.

Metformin therapy is associated with a RRR of 31%, which is also inferior to the 58% RRR obtained with diet and exercise.
The consensus panel has recommended that metformin therapy be considered in patients with both IFG and IGT, who constitute
a higher risk group. This patient does not have IGT (fasting plasma glucose level of 140 to 199 mg/dL [7.7 to 11.0 mmol/L]
at the 2-hour mark of an oral glucose tolerance test) and so should not receive metformin.

Modulators of the renin-angiotensin axis, such as ramipril and other angiotensin-converting enzyme inhibitors, were once thought
to contribute to diabetes prevention, but the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM)
study disproved this.

Rosiglitazone and pioglitazone have been associated, respectively, with 62% and 81% RRRs in the incidence of diabetes. However,
the consensus panel has not endorsed their routine pharmacologic use in patients with prediabetes because of their costs and
adverse effects, including edema, increased fracture risk in women, and possible increased cardiovascular morbidity.

Key Point

Patients with prediabetes should be advised to adopt a program of lifestyle change to prevent progression to type 2 diabetes
mellitus.

Test yourself

A 24-year-old woman undergoes routine evaluation. She is pregnant at 12 weeks' gestation. Medical history is notable for homozygous sickle cell anemia (Hb SS). She has had multiple uncomplicated painful crises treated at home with hydration, nonopioid analgesia, and incentive spirometry. Following a physical exam and lab studies, what is the most appropriate management?

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